Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus: Exploring potential role of miR-144-3p in zinc-induced insulin resistance. (February 2023)

• Record Type: Journal Article
• Authors: Ye, Zi; Cheng, Man; Fan, Lieyang; Ma, Jixuan; Zhang, Yingdie; Gu, Pei; Xie, Yujia; You, Xiaojie; Zhou, Min; Wang, Bin; Chen, Weihong
• Is Part Of: Environment international. Volume 172(2023)
• Publication Date: 2023-02
• Subjects: Zinc -- Type 2 diabetes mellitus -- MiR-144-3p -- Insulin resistance -- Nrf2; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2023.107807
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Plasma miRNAs expression profiles for zinc exposure and T2DM were identified. MiR-144-3p were positively associated with zinc exposure and T2DM risk. MiR-144-3p partially mediated zinc exposure-related hyperglycemia and T2DM. MiR-144-3p interacted with Nrf2 to regulate zinc-induced insulin resistance. Abstract: Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.